In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/32558 |
Resumo: | © 2016 American Society for Microbiology. All Rights Reserved. |
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In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residenceViral fusion inhibitorSelf-assembling nanoparticlesLipid taggingMembrane insertion© 2016 American Society for Microbiology. All Rights Reserved.Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo. We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The selfassembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides.This work was supported by NIH grants NS091263 (NINDS) and AI119762 and AI109050 (NIAID) to M.P. and AI101333 and AI114736-01 (NIAID) to A.M., Fundação para a Ciência e Tecnologia-Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) projects VIH/SAU/0047/2011 to A.S.V. and PTDC/BBB-BQB/3494/2014 to N.C.S., and INSERM and the LABEX ECOFECT (ANR-11-LABX-0048) of Lyon University, within the program “Investissements d’Avenir” (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR), to B.H. T.N.F. and A.S.V. acknowledge FCT for Ph.D. fellowship SFRH/BD/52383/2013 and fellowship IF/00803/2012 under the FCT Investigator Programme, respectively.American Society for MicrobiologyRepositório da Universidade de LisboaFigueira, T. N.Palermo, L. M.Veiga, A. S.Huey, D.Alabi, C. A.Santos, N. C.Welsch, J. C.Mathieu, C.Horvat, B.Niewiesk, S.Moscona, A.Castanho, Miguel A. R. B.Porottob, M.2018-04-03T11:45:28Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/32558engJ Virol 91:e01554-160022-538X10.1128/ JVI.01554-16info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:26:55Zoai:repositorio.ul.pt:10451/32558Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:47:50.113789Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence |
| title |
In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence |
| spellingShingle |
In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence Figueira, T. N. Viral fusion inhibitor Self-assembling nanoparticles Lipid tagging Membrane insertion |
| title_short |
In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence |
| title_full |
In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence |
| title_fullStr |
In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence |
| title_full_unstemmed |
In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence |
| title_sort |
In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence |
| author |
Figueira, T. N. |
| author_facet |
Figueira, T. N. Palermo, L. M. Veiga, A. S. Huey, D. Alabi, C. A. Santos, N. C. Welsch, J. C. Mathieu, C. Horvat, B. Niewiesk, S. Moscona, A. Castanho, Miguel A. R. B. Porottob, M. |
| author_role |
author |
| author2 |
Palermo, L. M. Veiga, A. S. Huey, D. Alabi, C. A. Santos, N. C. Welsch, J. C. Mathieu, C. Horvat, B. Niewiesk, S. Moscona, A. Castanho, Miguel A. R. B. Porottob, M. |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Figueira, T. N. Palermo, L. M. Veiga, A. S. Huey, D. Alabi, C. A. Santos, N. C. Welsch, J. C. Mathieu, C. Horvat, B. Niewiesk, S. Moscona, A. Castanho, Miguel A. R. B. Porottob, M. |
| dc.subject.por.fl_str_mv |
Viral fusion inhibitor Self-assembling nanoparticles Lipid tagging Membrane insertion |
| topic |
Viral fusion inhibitor Self-assembling nanoparticles Lipid tagging Membrane insertion |
| description |
© 2016 American Society for Microbiology. All Rights Reserved. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z 2018-04-03T11:45:28Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/32558 |
| url |
http://hdl.handle.net/10451/32558 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
J Virol 91:e01554-16 0022-538X 10.1128/ JVI.01554-16 |
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info:eu-repo/semantics/openAccess |
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openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
American Society for Microbiology |
| publisher.none.fl_str_mv |
American Society for Microbiology |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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